Methylphenidate (Ritalin) synthesis

[cokemuffin]

Would you get other esters of ritalinic acid if you'd do the last step in other solvents (IPA = isopropylphenidate, EtOH = ethylphenidate etc.)?

 

[G.Patton]

Would you get other esters of ritalinic acid if you'd do the last step in other solvents (IPA = isopropylphenidate, EtOH = ethylphenidate etc.)?

cokemuffinHi, yes, you will.

 

[cokemuffin]

oh i'm sorry that comment was meant for you. ever make 4f?

Chefy77What do you mean with 4f, i can not follow you?

 

[G.Patton]

Could you also do it with a ritalinic acid ester? I'd assume that as an example you could just hydrolyse methylphenidate HCl with NaOH in ipa to get the sodium salt of ritalinic acid, then just add hydrochloric acid to the solution to get isopropylphenidate HCl, saturate the solution with NaCl to push the IPH out of the water and let the solution form two layers, than decant the top layer and let the IPH crystallize from it (let the solvent evaporate). But that's just an assumption, so would that work?

cokemuffinHi. NaOH in IPA will completely spoil your ritalin*HCl. You can get ritalin freebase by aqueous NaOH and then carry out esterification.

 

[cokemuffin]

So would the process be to put the ritalin hcl in NaOH solution, get the ritalin freebase and then just put that in ipa to get isopropylphenidate? I'd guess the hcl should be added after esterfication to not replace the OH from the carboxyl group with a Cl, but i'm not 100% sure about that.

 

[G.Patton]

So would the process be to put the ritalin hcl in NaOH solution, get the ritalin freebase and then just put that in ipa to get isopropylphenidate? I'd guess the hcl should be added after esterfication to not replace the OH from the carboxyl group with a Cl, but i'm not 100% sure about that.

cokemuffinHello, sorry for a long reply. I haven't seen you question.

So would the process be to put the ritalin hcl in NaOH solution, get the ritalin freebase and then just put that in ipa to get isopropylphenidate?

No, eterefication isn't work like you describe. You have to get Ritalinic acid sodium salt and then get ester with IPA in acidic condition.

I'd guess the hcl should be added after esterfication to not replace the OH from the carboxyl group with a Cl, but i'm not 100% sure about that.

It won't work like you told =) What is a reason for these manipulations? Actually, I'm not sure that reaction will be sucsess. Moreover, you'll loose part of your ritalin.

 

[cokemuffin]

Hello, sorry for a long reply. I haven't seen you question.

No, eterefication isn't work like you describe. You have to get Ritalinic acid sodium salt and then get ester with IPA in acidic condition.

It won't work like you told =) What is a reason for these manipulations? Actually, I'm not sure that reaction will be sucsess. Moreover, you'll loose part of your ritalin.

G.PattonNever looked into eterefications, but if doing full synthesis appears to be the only viable option anyways, i guess i don't even have to. Instead i searched a bit more for routes to get methyl phenylglyoxylate. Thought about getting it from benzoyl chloride might be a good option, but i've only found syntheses that involve cyanides. Gringard reagents instead of cyanides would make it much safer but for some reason i couldn't find a synthesis of the reaction beneath anywhere?

I guess you could just replace benzyl chloride with benzoyl chloride and do the same reaction as you'd do to get PAA, but i'm not sure if there's something interfering.

 

[G.Patton]

Never looked into eterefications, but if doing full synthesis appears to be the only viable option anyways, i guess i don't even have to. Instead i searched a bit more for routes to get methyl phenylglyoxylate. Thought about getting it from benzoyl chloride might be a good option, but i've only found syntheses that involve cyanides. Gringard reagents instead of cyanides would make it much safer but for some reason i couldn't find a synthesis of the reaction beneath anywhere?

View attachment 9777
I guess you could just replace benzyl chloride with benzoyl chloride and do the same reaction as you'd do to get PAA, but i'm not sure if there's something interfering.

cokemuffinHello, there is oxygen. You can't carry out such synthesis.

 

[cokemuffin]

Hello, there is oxygen. You can't carry out such synthesis.

G.PattonFuck, now i at least know it interferes. benzoyl chloride and CuCN is the only way from benzoyl chloride then?

 

[G.Patton]

Fuck, now i at least know it interferes. benzoyl chloride and CuCN is the only way from benzoyl chloride then?

cokemuffinFor what? It is not PAA (phenylacetic acid).

 

[cokemuffin]

For what? It is not PAA (phenylacetic acid).

G.PattonIk, if you use benzyl chloride instead in the reaction above it gives you PAA. Thought using benzoyl chloride instead of benzyl chloride will give phenylglyoxylic acid, but since the oxygen interferes in the reaction the only way i know instead would be to use cyanides instead:

 

[Lordoftheshard]

I no this is a bit off topic I have a friend who has stick piled these tabs 10 mg
He asked me if there is any way you can extract the ritalin out of the tabs and make it into a smoke able form like meth

 

[G.Patton]

I no this is a bit off topic I have a friend who has stick piled these tabs 10 mg
He asked me if there is any way you can extract the ritalin out of the tabs and make it into a smoke able form like meth

LordoftheshardHi, acid/base extraction

 

[Lordoftheshard]

Hi, acid/base extraction

G.PattonThankyou sir as I tried normal Extractions first with ethanol doesn't matter if you filter and so forth end up blockers and other junk#. Coming over with it buy coincidence I seen your thread and though I would ask and brother thankyou this is the only way you can extract ritalin clean and properly I looked on Reddit and so forth I haven't seen any one elses as clean as this

 

[G.Patton]

Thankyou sir as I tried normal Extractions first with ethanol doesn't matter if you filter and so forth end up blockers and other junk#. Coming over with it buy coincidence I seen your thread and though I would ask and brother thankyou this is the only way you can extract ritalin clean and properly I looked on Reddit and so forth I haven't seen any one elses as clean as this

LordoftheshardAmphetamine purification by acid-base extraction I told about acid-base extraction, it is different procedure than you did. Read about it in this topic. Also, you can read about extraction procedure theory to understand what are you doing: Extraction

 

[Lordoftheshard]

Amphetamine purification by acid-base extraction I told about acid-base extraction, it is different procedure than you did. Read about it in this topic. Also, you can read about extraction procedure theory to understand what are you doing: Extraction

G.PattonI first dyd alcohol extracting bug blockers etc kept coming over with it
Then I did ab extraction to get this

 

[Lordoftheshard]

Thankyou

 

[toffifee]

Hello everywhere, can you help me find a marketplace to buy 1-Phenyl-2-(piperidin-1-yl)ethanone-1,2-dione. or Methyl phenylglyoxylate ? What is the best website for ordering reagents and laboratory equipment? CIS countries

 

[blackshwan]

Hello @G.Patton .


About this step (refluxing).
[The reaction mixture was gently refluxed for 3-12 hours with reflux condenser (as determined by monitoring by TLC). ]


What is the temperature of the heat souce? Thanks.

https://bbgate.com/attachments/lwndic7fo8-png.2904/

What is "heating under reflux"?

When dealing with organic reactions, heating under reflux is often required, such as the oxidation of Toluene using acidified $\ce{KMnO4}$ and dilute $\ce{H2SO4}$ to Benzoic acid($\ce{C6H6O2})$ What

chemistry.stackexchange.com

 

[G.Patton]

Hello @G.Patton .


About this step (refluxing).
[The reaction mixture was gently refluxed for 3-12 hours with reflux condenser (as determined by monitoring by TLC). ]


What is the temperature of the heat souce? Thanks.

https://bbgate.com/attachments/lwndic7fo8-png.2904/

What is "heating under reflux"?

When dealing with organic reactions, heating under reflux is often required, such as the oxidation of Toluene using acidified $\ce{KMnO4}$ and dilute $\ce{H2SO4}$ to Benzoic acid($\ce{C6H6O2})$ What

chemistry.stackexchange.com

blackshwanHello. The temperature, which would be enough to boil the mixture of 1-phenyl-2-(piperidin-1-yl)ethane-1,2-dione (1) in dimethoxyethane was added p-toluenesulfonhydrazide (2) (1.1 equivalent) at normal conditions (22*C, 760 mm Hg).

 

[dupskoslonia]

Hey guys. I have ritalinic acid. What do I need to make metylphenidate and etylphenidate? I'm a complete newbie, could you please explain me step by step? Would be really grateful

 

[HerrHaber]

Hey guys. I have ritalinic acid. What do I need to make metylphenidate and etylphenidate? I'm a complete newbie, could you please explain me step by step? Would be really grateful

dupskosloniaYou need to convince your carbonyl group to make an ester with methanol and ethanol respectively. This is pretty straight forward by standard chemical means and try looking for rather mild methods such as enzymes (lipases) or easy to work with ClSiMe3 in methanol with substrate.

 

[kotkata]

Hey guys. I have ritalinic acid. What do I need to make metylphenidate and etylphenidate? I'm a complete newbie, could you please explain me step by step? Would be really grateful

dupskosloniaIs there a protocol or beginner's guide or recipe of some sort to convert ritalinic acid to methylphenidate?

To my understanding it's not rocket, but I'm a bit confused how to get methylphenidate from ritalinic acid.

 

[SmartResearcher]

Is there a protocol or beginner's guide or recipe of some sort to convert ritalinic acid to methylphenidate?

To my understanding it's not rocket, but I'm a bit confused how to get methylphenidate from ritalinic acid.

kotkataHello everybody! Replying for dupskoslonia, I add recipe for methylphenidate hydrochloride from dl-threo-ritalinic acid (which is easy avaliable in China, price for 1 kg is about 600-700$). I made dl-threo-methylphenidate hydrochloride a few times of this recipe and it's absolutely easy and perfect. 1 kg of methylphenidate hydrochloride, you can do in 20L single-neck flask (you don't need reactor).

125g (0.57 mol) of dl-threo-ritalinic acid added to reactor. Then added 256.7g (5 mol) of dimethyl carbonate and 27.5g methanol. Then at room temperature with mechanical stirrer (magnetic stirrer is not good to this operation) slowly added 762g of 96% or more of sulphuric acid (temperature <80oC). The jacket temperature was increased to 85oC (target internal temperature about 70oC). The reaction was stirred overnight (at least 16 hours) at a jacket temperature of 85oC.

The resulting mixture was then cooled to 15-20oC. To the resulting mixture was then added 250g of isopropyl acetate followed by addition of 18% NaOH (212.5g, 1.68 mol), while maintaining the temperature below at 30oC. Then, the mixture stirred for about 15 minutes. The layers were allowed to settle for about 20 minutes and the lower, caustic (aqueous) layer separated and discarded. To the organic layer was then added deionized water (187.5g) and the resulting mixture stirred for about 20 minutes. The layers were allowed to settle for about 20 minutes and the lower, water layer seperated and discarded. The organic layer, contain dl-threo-methylphenidate.

A second reactor was charged with the solution of 37% HCl (59g, 1.05 mol) and IPA (250g). The internal temperature of the solution was adjusted to 55oC. To this reactor was then added the organic layer containing dl-threo-methylphenidate, prepared in STEP1, via addition funnel over 90 minutes, while maintaining the temperature at 55oC. Then the mixture was cooled to 10-15oC and stirred for 30 minutes. The resulting suspension was filtered through a Buchnner funnel and the wet cake washed with IpOAc (125g). Achieved about 110-125g of dl-threo-methylphenidate hydrochloride (exactly the same isomer like in pharmacy).

 

[kotkata]

Hello everybody! Replying for dupskoslonia, I add recipe for methylphenidate hydrochloride from dl-threo-ritalinic acid (which is easy avaliable in China, price for 1 kg is about 600-700$). I made dl-threo-methylphenidate hydrochloride a few times of this recipe and it's absolutely easy and perfect. 1 kg of methylphenidate hydrochloride, you can do in 20L single-neck flask (you don't need reactor).

125g (0.57 mol) of dl-threo-ritalinic acid added to reactor. Then added 256.7g (5 mol) of dimethyl carbonate and 27.5g methanol. Then at room temperature with mechanical stirrer (magnetic stirrer is not good to this operation) slowly added 762g of 96% or more of sulphuric acid (temperature <80oC). The jacket temperature was increased to 85oC (target internal temperature about 70oC). The reaction was stirred overnight (at least 16 hours) at a jacket temperature of 85oC.

The resulting mixture was then cooled to 15-20oC. To the resulting mixture was then added 250g of isopropyl acetate followed by addition of 18% NaOH (212.5g, 1.68 mol), while maintaining the temperature below at 30oC. Then, the mixture stirred for about 15 minutes. The layers were allowed to settle for about 20 minutes and the lower, caustic (aqueous) layer separated and discarded. To the organic layer was then added deionized water (187.5g) and the resulting mixture stirred for about 20 minutes. The layers were allowed to settle for about 20 minutes and the lower, water layer seperated and discarded. The organic layer, contain dl-threo-methylphenidate.

A second reactor was charged with the solution of 37% HCl (59g, 1.05 mol) and IPA (250g). The internal temperature of the solution was adjusted to 55oC. To this reactor was then added the organic layer containing dl-threo-methylphenidate, prepared in STEP1, via addition funnel over 90 minutes, while maintaining the temperature at 55oC. Then the mixture was cooled to 10-15oC and stirred for 30 minutes. The resulting suspension was filtered through a Buchnner funnel and the wet cake washed with IpOAc (125g). Achieved about 110-125g of dl-threo-methylphenidate hydrochloride (exactly the same isomer like in pharmacy).

SmartResearcherAwesome, thank you so much, @dupskoslonia!

Really appreciated!!